Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

Abstract

The paracrine effect, mediated by chemical signals that induce a physiological response on neighboring cells in the same tissue, is an important regenerative mechanism for stem cell-based therapy. Exosomes are cell-secreted nanovesicles (50-120 nm) of endosomal origin, and have been demonstrated to be a major contributor to the observed stem cell-mediated paracrine effect in the cardiac repair process. Following cardiac injury, exosomes deriving from exogenous stem cells have been shown to regulate cell apoptosis, proliferation, angiogenesis, and fibrosis in the infarcted heart. Exosomes also play a crucial role in the intercellular communication between donor and recipient cells. Human induced pluripotent stem cells (hiPSCs) are promising cell sources for autologous cell therapy in regenerative medicine. Here, we review recent advances in the field of progenitor-cell derived, exosome-based cardiac repair, with special emphasis on exosomes derived from hiPSCs.

Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy

“…Recent studies confirmed that exosomes repaired tissue damage and inhibited tissue degeneration by inhibiting apoptosis and inflammation 41‐44 . Based on the GO analysis of proteins carried in exosomes, we also found that N‐Exos may inhibit IVDD by inhibiting NPC apoptosis.…”

Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia

“…34 Accumulating evidence suggests exosomes secreted from different cell types carry vast different varieties of bioactive molecular cargoes and subsequently provide different biological responses. 35 For instance, exosomes secreted from human CD34 + stem cells, which were isolated from peripheral blood mononuclear cells, promoted the repair of the ischemic hindlimb. 28 The exosomes derived from CD34 + cells contain proangiogenic miRNAs, such as miR-126-3p, which enhance angiogenesis by regulating the expression of pro-angiogenic genes, including VEGF, angiopoietins, and matrix metallopeptidase 9.…”

“…Many studies have demonstrated that MSC stimulates neovascularization and blood perfusion in ischemic tissues by secreting pro‐angiogenic cytokines and growth factors, including VEGF, FGF‐2, HGF, and IGF‐1 34 . Accumulating evidence suggests exosomes secreted from different cell types carry vast different varieties of bioactive molecular cargoes and subsequently provide different biological responses 35 . For instance, exosomes secreted from human CD34 + stem cells, which were isolated from peripheral blood mononuclear cells, promoted the repair of the ischemic hindlimb 28 .…”

Roles and Clinical Applications of Exosomes in Cardiovascular Disease

“…Other Stem Cell-Derived Exosomes. Exosomes secreted by induced pluripotent stem (iPS) cells protect the heart against multiple stress [61]. iPS cell-derived exosomes enhance the autophagic flux by inhibiting mTOR pathway and promoting cardiomyocyte survival both in vitro and in vivo [62].…”